Functions of IL-1alpha and ESE-1 in Reactive Stroma Modulation of the Immune Landscape in Prostate Cancer
Technical Report,01 Sep 2017,31 Aug 2018
Baylor College of Medicine Houston United States
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The purpose of this project is to understand the role and mechanisms of IL-1alpha in regulating the ontogeny and differentiation of mesenchymal stem cells MSCs to immune reactive fibroblasts in prostate cancer. Aim 1 is to address ontogeny of immune reactive fibroblasts from perivascular MSCs. Aim 2 is to address the role of the ELF3 transcription factor. Aim 3 is to address how the recruitment and biology of immune reactive fibroblasts regulate the immune landscape in experimental tumors. Progress has been made in engineering prostate cancer cells for overexpression of IL-1alpha and in knocking down ELF3 expression in MSCs. We have generating three-dimensional organoids as proposed. We have also generated the NG2-creEsr1 R26-stop-EYFP and the NG2-creEsr1 R26-stop-EYFP Elf3 flfl mice, which have now been backcrossed 10 generations into the C57BL6 background. We have been successful in generating allograft tumors of TRAMP C1D cancer cells in the reporter mice. We were able to show that perivascular MSCs are the source of the IL-1alpha induced fibroblasts in vivo and that ELF3 mediates IL-1alpha action. Progress has been made in each Aim.
- Medicine and Medical Research